The overall goal of this renewal application is to improve the effectiveness of positron emisskm tomography (PET) imaging for the diagnosis and treatment of patients with cancer. The proposed research will compare the performance of several alternative scanner designs for tumor quantitation and detection tasks commonly performed in our clinical and research PET protocols. The target applications include tumor imaging in the breast and torso using 18F-estradiol, '8FDG, and "C-thymidine, for tumor detection and staging, therapy planning, and monitoring response to therapy. The scanner designs considered will include existing 2D and 3D systems, as well as new designs with varying axial and radial extent, coarse collimation, and different scintillator materials. Additional research will evaluate the difficulties confronting PET using several isotopes that have recently attracted significant interest for a variety of applications, but which decay by complicated pathways and produce background radiation (e.g. increased randoms, septal penetration, and, for some isotopes, pair production) that ultimately contaminates the image data. Methods to compensate for these effects will be developed and evaluated. The applications for the isotopes considered, 86Y, 1241, and 94mTc, include therapy planning prior to treatment with monoclonal antibodies and cross-validation studies for quantitative SPECT performed with 99mTc-based compounds. As part of previous research conducted at the University of Washington, a Simulation System for Emission Tomography (SimSET) was developed. This Monte Carlo-based software package tracks photons through complex heterogeneous objects (patients) and models the effects of collimation and detection. The research proposed in this application will require several improvements and extensions to SimSET. New tools to automate the measurement of image quality will be added. A number of new acceleration techniques will be incorporated, as well as models for additional physical effects. This work, along with continuing efforts to make the software easier to use, will also support ongoing research by the many other investigators using SimSET at other institutions. The SimSET software package is freely available via the Internet.